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Biomedical subjects

W K Hong

Publications and source records attributed to W K Hong.

At least 343 records · Page 19Linked to original sources
PubMed1990

Superior antiproliferative effects mediated by interferon-alpha entrapped in liposomes against a newly established human lung cancer cell line.

The purpose of this study was to characterize the antiproliferative activity of a recombinant interferon-alpha (IFN-alpha) against a newly established human adenocarcinoma cell line (DMS-4C) and to determine whether IFN-alpha entrapped in multilamellar liposomes had superior antitumor effects compared with free IFN-alpha. Treatment of DMS-4C cells with 100 U/ml of free IFN-alpha resulted in 34% cytostasis. IFN-alpha encapsulated in phosphatidylcholine/phosphatidylserine multilamellar vesicles produced growth inhibition of 67%, which was significantly greater than that produced by free IFN-alpha or by control liposomes containing only medium combined with free IFN-alpha. Moreover, kinetic analysis revealed that to produce significant cytolysis, free IFN-alpha had to be incubated with target cells for at least 24 h, whereas IFN-alpha encapsulated into liposomes required only 30 min of exposure.

Adenocarcinoma↗
PubMed1989

Effect of retinoic acid on DNA cleavage and cytotoxicity of topoisomerase II-reactive drugs in a human head and neck squamous carcinoma cell line.

Evidence from several in vitro systems indicates that cellular responses to DNA topoisomerase II-reactive compounds (i.e., the epipodophyllotoxins and intercalating agents) may be affected by the relative rate of proliferation. Using a human head and neck squamous carcinoma cell line 183A, we have investigated the effect of beta-all-trans-retinoic acid (RA), a substance with known antiproliferative effects, on the DNA cleavage and cytotoxic activities of etoposide and 4'-(acridinylamino)methanesulfon-m-anisidide which interact with topoisomerase II. The effect of RA treatment on the activity of X-radiation and bleomycin, both of which produce free radical mediated effects, was also examined. RA treatment (10 to 20 microM for 72 h) does not significantly influence DNA cleavage induced by X-radiation or bleomycin but decreases DNA cleavage and cytotoxicity mediated by etoposide and 4'-(acridinylamino)methanesulfon-m-anisidide. Further, this effect can be demonstrated at a dose of RA that is minimally growth inhibitory. The inhibitory effect of RA appears to be localized to the nucleus given that similar effects on drug-mediated DNA cleavage can be demonstrated in nuclei isolated from RA-treated cells. However, both drug-stimulated DNA cleavage activity and topoisomerase II catalytic activity are approximately equal in crude nuclear extracts of untreated and RA-treated cells. These data suggest that the resistance to topoisomerase II-reactive drugs induced by RA treatment of 183A cells is not mediated through a direct effect on the enzyme, but, instead, is related to other changes in the nuclear milieu occurring in the initial stages of quiescence such as altered chromatin conformation.

Amsacrine↗
PubMed1989

Advanced basal cell carcinoma and successful treatment with chemotherapy.

The patient presented in this report has a large basal cell carcinoma on the wrist and thigh. The lesion on the wrist was nonresectable without amputation. The patient showed an impressive response to chemotherapy with systemic cyclophosphamide, adriamycin, and intra-arterial cisplatin. The tumor could be excised by a simple excision on both sites and showed no residual tumor on the hand and only a microscopic focus on the thigh. The patient continues to be free of disease 3 years after the initiation of the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection.

Sixty-six patients with disseminated malignancy were treated with recombinant interleukin-2 (IL-2) on a three times a week (M, W, F) IV-bolus injection schedule. Doses ranged from 0.001 to 14.0 x 10(6) units/M2 body surface area. Consecutive groups of 3-5 patients were placed on each dose level and were maintained on that level except for dosage de-escalation for toxicity. Toxicity to all major organ systems were noted with major toxicity including fever and chills, anorexia, fatigue and malaise, arthralgias and arthritis as well as hepatic and renal toxicity. All toxicity reversed within one week of drug cessation. Renal toxicity manifested by azotemia, arthritis and fatigue were the common dose limiting toxicities and the maximally tolerated dose was 12 x 10(6) units/M2. Pharmacokinetic studies indicated a short half-life (T1/2 alpha = 7-23 minutes). At doses over 0.5 x 10(6) units/M2 increases in absolute lymphocytes and eosinophil counts were noted. All T lymphocyte subsets increased. Maximal increases were seen at 4-8 x 10(6) units/M2 with a lesser increase at 10-14 x 10(6) units/M2 dosage level. Circulating NK cells also increased while circulating LAK cells were detected during therapy. Partial responses were noted in 3 patients with melanoma. These lasted 4, 6 and 16 months and involved pulmonary, pulmonary plus mesenteric and retro-orbital plus hepatic metastases respectively in these patients.

Drug Evaluation↗
PubMed1989

Multiple primary cancer in patients with cancer of the head and neck: second cancer of the head and neck, esophagus, and lung.

Squamous cell carcinoma of the head and neck is complicated by a second primary carcinoma of the head and neck, esophagus (the upper aerodigestive tract, or UADT), or lung in 10-40% of patients. Routine panendoscopy will identify a simultaneous second primary in 9-14% of the patients. Metachronous second cancers most often involve the esophagus or lung, whereas synchronous second cancers are more common in the head and neck as occult lesions. For the highest-risk subgroups, second primary cancers occur in 4% of patients per year. In cancer of the floor of the mouth the excess mortality rate is 5-6% per year. Risk is independent of stage of the first primary and the survival impact is the greatest in groups of patients with early-stage disease. Head and neck cancer almost always results from the heavy use of tobacco for many years, either with or without the concomitant heavy use of alcohol, and these same agents are directly responsible for the second cancers of the UADT and lung. All head and neck cancer patients should be advised to avoid these agents. The clinician must diagnose and treat second cancers to extend the survival of patients with a good prognosis for control of the initial head and neck cancer. We need further progress in eliminating the use of known carcinogens in these patients, paradigms for cost-effective diagnosis and treatment of second primary cancers, effective treatment of the head and neck primary cancer devoid of long-lasting tissue toxicities, effective chemopreventive agents to retard established processes of carcinogenesis that place the patient at continued risk after cigarette and alcohol use has been eliminated, and continued efforts to control the medical illnesses to which these patients are susceptible.

Carcinoma, Squamous Cell↗
PubMed1989

Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group.

A total of 353 patients with previously untreated small-cell lung cancer (SCLC) were accrued in this multicenter trial. Patients were randomly assigned to receive one of the following three regimens: cyclophosphamide 1,000 mg/m2 intravenously (IV) day 1, vincristine 1.4 mg/m2 IV day 1, and etoposide 50 mg/m2 IV day 1, followed by etoposide 100 mg/m2/day orally days 2 through 5 (CEV); cyclophosphamide 1,000 mg/m2 IV day 1, vincristine 1.4 mg/m2 IV day 1, and doxorubicin 50 mg/m2 IV day 1 (CAV); cyclophosphamide 2,000 mg/m2 day 1 and vincristine 1.4 mg/m2 IV day 1 (CV). Cycles were repeated every 3 weeks. Treatment groups were comparable with respect to extent of disease, age, sex, performance status, and metastatic sites. No significant differences in response rates, response duration, or survival could be detected in limited disease, although there appeared to be a trend favoring CEV. Among extensive-disease patients, response duration on the CEV regimen was longer than on the CV regimen or the CAV program (P less than .001). The superiority of the CEV regimen was also demonstrated in the survival analysis in which differences attained statistical significance (P = .01). In this group the median survival was increased from 29 weeks on CV to 31 weeks on CAV and 39 weeks on CEV. Myelosuppression was the most frequent toxicity. It was more severe with CV than CEV or CAV. Most nonhematologic side effects were comparable among the three treatment groups. However, the high doses of cyclophosphamide in the CV regimen produced a higher incidence of hemorrhagic cystitis than in the CEV or CAV programs (P less than .001). Cardiotoxicity only occurred in the CAV group (P = .05). The addition of etoposide to the CV regimen resulted in significantly longer response duration and survival without increased toxicity. Similarly, the substitution of etoposide for the doxorubicin in the CAV regimen was associated with prolonged survival and reduced cardiotoxicity.

Adult↗
PubMed1989

Immunologic determinants of head and neck cancer response to induction chemotherapy.

Various measures of immune response were assessed prior to induction chemotherapy (intravenous [IV] cisplatin, fluorouracil [5-FU], and bleomycin) in 43 previously untreated head and neck cancer patients to derive a clinical response prediction model. These were parameters of functional cellular immunity (natural killer [NK] cell activity, lymphocyte blastogenesis response to mitogens), total lymphocyte and lymphocyte subset numbers and percentages, and circulating humoral immunity (total immunoglobulin, immunoglobulin classes, and C1q binding activity [C1q BA]). The C1q BA may reflect levels of circulating immune complexes within peripheral blood. The objective primary tumor response rate was 65% (16 complete responses and 12 partial responses). Univariate logistic regression analysis showed that failure to respond to therapy was significantly related to higher value (vis-à-vis response) of humoral immune parameters total immunoglobulin (Ig), P less than .01; IgG, P less than .01; and C1q BA, P less than .001. No association between cellular immune response measurements and response to chemotherapy was identified. By multivariate logistic regression analysis, only C1q BA levels were predictive of drug therapy responsiveness (P less than .001). Results extend our previous investigations regarding C1q BA measurement in head and neck cancer patients, and show that C1q BA levels add accuracy of prediction of subsequent chemotherapy response to that based solely on standard staging criteria and other parameters of immune status.

Adult↗
PubMed1989

Primary chemotherapy of brain metastasis in small-cell lung cancer.

Fourteen patients with brain metastases from previously untreated small-cell lung cancer (SCLC) were treated with three courses of systemic chemotherapy as an initial mode of treatment. Whole brain irradiation was given concurrently with the fourth course of chemotherapy. The chemotherapy consisted of cyclophosphamide, 600 mg/m2 intravenously (IV) on day 1; doxorubicin, 50 mg/m2 IV on day 1; vincristine, 1.5 mg IV days 1 and 5; and etoposide, 60 mg/m2 IV days 3 through 5; all repeated every 3 weeks with dosage adjustments. There were ten men and four women, with a median age of 59 years (range, 47 to 75). Six patients had multiple brain lesions, and the brain was the sole site of distant metastasis in four patients. Three patients were inevaluable for response in the brain, as two died early and the third dropped out of the trial too soon. Brain lesions responded to chemotherapy in nine (one complete remission [CR], eight partial remissions [PR]) of 11 (82%) evaluable patients, and objective responses in the extracranial lesions were documented in nine (one CR, eight PR) of 12 (75%) evaluable patients. Median survival was 34 weeks (range, 1 to 93), and two patients are still alive. Toxicity was significant, with severe granulocytopenia (less than 500/microL) and thrombocytopenia (less than 50,000/microL) observed in 85% and 15% of patients, respectively. Six patients had major infectious complications, which resulted in septic deaths in two. However, there was no deterioration of neurologic status during the initial phase of treatment with chemotherapy. We conclude that systemic chemotherapy alone can induce objective regression of metastatic brain lesions in patients with previously untreated SCLC.

Aged↗
PubMed1989

Recombinant interferon-gamma in the treatment of recurrent nasopharyngeal carcinoma.

The etiologic relationship of the Epstein-Barr virus (EBV) to nasopharyngeal carcinoma prompted this study of the efficacy of interferon-gamma (IFN-gamma), which possesses antiviral and antitumor activity, in the treatment of recurrent carcinoma. Fourteen patients received recombinant IFN-gamma in daily intramuscular doses of 5-10 X 10(6) U/m2. Of 13 patients evaluable for response, five had a minor response; disease was stable in two and had progressed in six. EBV serology for immunoglobin (Ig) G, IgA-VCA, and early antigen was measured in six patients. In four of these, titers rose consistently with disease progression and in one patient, titers decreased with minor response.

Adult↗
PubMed1988

Association of levels of circulating C1q binding macromolecules with induction chemotherapy response in head and neck cancer patients.

Ninety-five untreated patients with squamous cell carcinoma of the upper aerodigestive tract expressed significantly higher levels of C1q-binding macromolecules as compared to 45 noncancer-bearing controls. No relationship between C1q-binding macromolecules and levels of circulating IgG-immune complexes as determined by the solid-phase C1q-binding assay or the C3d-solid-phase assay could be defined suggesting that C1q-binding macromolecules were distinct from IgG-circulating immune complexes. An elevated level of C1q-binding macromolecules within these patients was predictive of subsequent response to induction chemotherapy; those with elevated levels characteristically showed no response. Using multivariate logistic regression analysis including the covariates of American Joint Committee staging parameters as well as C1q assay results, levels of the isolated macromolecules added significant prognostic information as to the probability of chemotherapeutic response. The quantitation of C1q macromolecules has clinical implication as to choice of therapeutic regimens against head and neck cancer. The nature of these substances remains to be defined.

Adult↗
PubMed1988

Reduction to homozygosity at the SIS/PDGF-2 locus in human mesenchymal tumors.

Enhanced expression of the human SIS/PDGF-2 gene has been reported in a number of human cell lines, sarcomas, and glioblastomas. We have analyzed the SIS/PDGF-2 gene for structural alterations in fresh human tumors. DNA samples from 79 patients with solid tumors (63 mesenchymal tumors, 12 lung carcinomas, 4 breast carcinomas) were examined and compared with DNA samples from 50 leukemia patients and 14 unrelated individuals without malignant neoplasms. When DNA samples were digested with a HindIII restriction endonuclease, Southern blot analysis demonstrated two distinct bands (21kb and 18kb) after hybridization to the SIS/PDGF-2 gene probe. A pedigree analysis of a 43-member family indicated that these allelic variants segregated in a Mendelian fashion. There was, however, tumor specific allele loss in 18% of the mesenchymal tumors analyzed, which may indicate a common etiology for this tumor type.

Cell Line↗
PubMed1988

Association of the Epstein-Barr virus with lymphoepithelioma of the thymus.

A 30-year-old woman with the histologic diagnosis of lymphoepithelioma of the thymus is reported on. Investigation of Epstein-Barr serology showed evidence of infection, and Southern blot analysis showed the presence of the viral genome in the tumor specimen. The patient achieved complete remission after treatment with combination chemotherapy, autologous bone marrow transplant, and radiotherapy. These findings suggest that lymphoepithelioma of the thymus may have a viral pathogenesis similar to that of nasopharyngeal carcinoma.

Adult↗
PubMed1988

Continuous cisplatin (24-hour) and 5-fluorouracil (120-hour) infusion in recurrent head and neck squamous cell carcinoma.

Cisplatin and 5-fluorouracil (5-FU) has been reported to be one of the most active chemotherapeutic regimens in recurrent head and neck squamous cell carcinoma. In this study, 21 patients with recurrent head and neck squamous cell carcinoma received a combination of cisplatin given as a 100 mg/m2 continuous infusion over 24 hours and 5-FU given as a 1000 mg/m2 24-hour continuous infusion for 120 hours. Toxicity was evaluated in all patients, and response and survival were evaluated 20 patients. There were two complete remissions (10%) and three partial remissions (15%) for a major response of 25%. Overall survival for the complete responders was 79+ and 61+ weeks, respectively. Median survival for all patients was 36 weeks. Toxicity consisted of moderate to severe nausea and vomiting in 14 patients (66%), mucositis in 14 patients (66%), granulocytopenia of less than 1000/microliter in 11 patients (52%), objective peripheral neuropathy in one patient (4.7%), and nephrotoxocity in one patient (4.7%). We conclude that the efficacy of 24-hour cisplatin infusion and 120-hour 5-FU infusion in the treatment of recurrent head and neck squamous carcinoma is not superior to the efficacy of single agent trials reported in the literature.

Adult↗
PubMed1988

Squamous cell carcinoma of the upper aerodigestive tract. A case comparison analysis.

Although the etiologic importance of tobacco in risk of upper aerodigestive malignancies is unquestioned, quantification of subsite-specific risks is less well delineated. Risk estimates from this case-control study are derived from self-administered comprehensive risk factor questionnaires distributed to newly registered patients at The University of Texas M.D. Anderson Hospital and Tumor Institute, Houston. Cases included 185 white patients with histologically confirmed squamous cell carcinoma of the upper aerodigestive tract. An equal number of age-frequency and sex-frequency matched patients was randomly selected from the same patient population excluding only patients with diagnoses of squamous cell carcinoma of any site. A statistically significant dose-response relationship for three categories of cigarette pack-years was evident for both males (odds ratios [OR] = 1.8, 4.0, and 7.5) and females (OR = 1.5, 9.0, and 12.0). Highest risks were documented for laryngeal cancer (OR = 15.1) and lingual cancer (OR = 14.5). There was interaction between alcohol use and smoking among men, but no independent effect of alcohol consumption among either gender. After 15 years of smoking abstinence, males no longer exhibited increased risk (OR = 1.0) whereas the risk for females after 15 years of cessation was 1.5. There were also significantly increased risks among men associated with snuff dipping, cigar, and pipe use (OR = 3.4, 2.8, and 1.8, respectively). The differences in the magnitude of the risk estimates and dose-response curves by subsite and by sex suggest a variable susceptibility to carcinogenic action.

Adult↗
PubMed1988

Prospective randomized trial of high-dose cisplatin and fluorouracil infusion with or without sodium diethyldithiocarbamate in recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Previous studies have indicated that sodium diethyldithiocarbamate (DDTC) can reduce cisplatin's (CP) toxic effects without altering the antitumor activity. DDTC has also been shown to have immunostimulative properties. Sixty patients with objectively measurable recurrent and/or metastatic squamous cell carcinoma (SCC) of the head and neck were randomized to receive either (A) CP at 120 mg/m2 over one hour on day 1, plus fluorouracil (5-FU) at 1,000 mg/m2 over 24 hours as a continuous infusion on days 1 through 5, or (B) CP/5-FU as in A, plus DDTC at 600 mg/m2 over 30 minutes administered intravenously (IV) exactly 30 minutes after CP infusion. Group B also received DDTC at 200 mg/m2 administered IV over 30 minutes on days 8 and 15. Each cycle was repeated at 3-week intervals. Objective responses were achieved in 41% of the CP/5-FU group and in 29% of the CP/5-FU with DDTC group (P = .26). Median survival was 9 months in group A and 10 months in group B. CP-related toxicity between the groups was equivalent with respect to nausea and vomiting, renal impairment, neurotoxicity, ototoxicity, and hematologic toxicity. The pharmacokinetics of reactive platinum species in plasma ultrafiltrate and urine samples obtained from both groups were comparable. The immune status of 48 patients was evaluated before and after completion of therapy. There were no significant differences in mean pretreatment and posttreatment values within or between groups A or B, except for absolute pretreatment OKT4 values (P = .02). We conclude that (1) the present dose and infusion schedule of DDTC did not significantly reduce CP-mediated toxic effects, (2) DDTC did not alter the disposition of ultrafilterable platinum species, (3) DDTC did not affect immune responses, and (4) the addition of DDTC improved neither the clinical response nor the survival of patients with recurrent SCC of the head and neck.

Adult↗